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B Crain

Publications and source records attributed to B Crain.

34 records · Page 2Linked to original sources
PubMed1987

Pertussis toxin blocks depressant effects of opioid, monoaminergic and muscarinic agonists on dorsal-horn network responses in spinal cord-ganglion cultures.

After chronic exposure of mouse spinal cord-ganglion explants to morphine, the acute depressant effects of opioids on sensory-evoked dorsal-horn network responses are markedly attenuated, and characteristic cord discharges can then occur even in the presence of greater than 100-fold higher opioid concentrations. The present study demonstrates that a remarkably similar degree of tolerance to opioids develops in these cord-ganglion explants after exposure to pertussis toxin (PTX). The usual acute depressant effects of serotonin, norepinephrine and oxotremorine on dorsal-horn discharges are also similarly attenuated in PTX-treated cultures. PTX is known to interfere with the guanine nucleotide protein Gi that is required for opioid, alpha 2-adrenergic and muscarinic receptor-mediated inhibition of adenylate cyclase in various cells. We have previously found that in cord-dorsal root ganglion explants agents which elevate intracellular cAMP also attenuate opioid depressant effects. Furthermore, these explants contain an opioid-inhibited adenylate cyclase system, and chronic exposure to morphine as well as PTX increases adenylate cyclase activity. These findings together with the present results suggest that the neuromodulatory effects of opioid, monoaminergic and muscarinic agonists on primary afferent networks in the spinal cord may be mediated by binding to neuronal receptor subtypes that are negatively coupled via Gi to a common pool of adenylate cyclase.

Adenylate Cyclase Toxin↗
PubMed1986

Cyclic AMP or forskolin rapidly attenuates the depressant effects of opioids on sensory-evoked dorsal-horn responses in mouse spinal cord-ganglion explants.

Exposure of fetal mouse spinal cord-ganglion explants to morphine (greater than 0.1 microM) results in naloxone-reversible, dose-dependent depression of sensory-evoked dorsal-horn synaptic-network responses within a few minutes. After chronic opiate exposure (1 microM) for 2-3 days, these dorsal cord responses recover and can then occur even in greater than 10 microM morphine. In the present study, when naive explants were treated with forskolin (10-50 microM)--a selective activate activator of cyclase (AC)--for 10-30 min prior to and during exposure to morphine (0.1-0.3 microM) or D-Ala2-D-Leu5-enkephalin (0.03-0.1 microM), the usual opioid depressant effects on dorsal-horn responses generally failed to occur (10-30 min tests). Dibutyryl cyclic AMP (10 microM) or the more lipid-soluble analog, dioctanoyl cyclic AMP (0.1 mM), produced a similar degree of subsensitivity to opiates as 10 microM forskolin. With high levels of forskolin (50 microM), even concentrations of morphine up to 1-10 microM were far less effective in depressing cord responses. These effects of exogenous cAMP analogs and forskolin on cord-ganglion explants are probably both mediated by increases in intracellular cAMP. The marked decrease in opioid sensitivity of cAMP or forskolin-treated cord-ganglion explants provides significant electrophysiologic data compatible with the hypothesis that neurons may develop tolerance and/or dependence during chronic opioid exposure by a compensatory enhancement of their AC/cAMP system following initial opioid depression of AC activity. Previous evidence relied primarily on behavioral tests and biochemical analyses of cell cultures. It will be of interest to determine if dorsal-horn tissues of cord-ganglion explants do, in fact, develop increased AC/cAMP levels as they express physiologic signs of tolerance during chronic exposure to opioids.

Animals↗
PubMed1986

Pertussis toxin treatment results in tolerance to the depressant effects of opioid, monoaminergic, and muscarinic agonists on dorsal-horn network responses in mouse spinal cord-ganglion cultures.

After treatment of mouse spinal cord-ganglion explants with pertussis toxin (PTX), the acute depressant effects of opioids on sensory-evoked dorsal-horn network responses are markedly attenuated, and characteristic cord discharges can then occur even in the presence of greater than 100-fold higher opioid concentrations, as observed after chronic exposure to opioids. The usual acute depressant effects of serotonin, norepinephrine, and oxotremorine on dorsal-horn discharges are similarly attenuated in PTX-treated cultures. These results together with our previous physiologic and biochemical analyses of adenylate cyclase (AC) and cyclic AMP (cAMP) activities in cord-ganglion cultures suggest that the neuromodulatory effects of opioid, monoaminergic and muscarinic agonists on primary afferent networks in the spinal cord may be mediated by binding to neuronal receptor subtypes that are negatively coupled via Gi to a common pool of AC.

Adenylate Cyclase Toxin↗
PubMed1982

Exposure to 4-aminopyridine prevents depressant effects of opiates on sensory-evoked dorsal-horn network responses in spinal cord cultures.

The depressant effects of morphine (0.1-1 microM) on sensory-evoked dorsal-horn network responses in explants of mouse spinal cord with attached dorsal root ganglia (DRGs) were rapidly restored after addition of 4-aminopyridine (4-AP; 0.1 mM) and major components of these cord responses were stably maintained in the presence of the opiate. Moreover, prior exposure of cord-DRG explants to 0.1 mM 4-AP prevented the depressant effects of 0.1 microM morphine on DRG-evoked dorsal-horn responses, and the effects of 1-10 microM morphine were at least partly antagonized. Increased Ca++ levels (5 microM) attenuated the depression of dorsal horn responses by 1-10 micro M morphine and these effects of Ca++ were greatly enhanced in the presence of 4-AP--in some cultures, concentrations of morphine as high as 100 micro M were strongly antagonized during test periods up to 2 hours. Receptor assays showed that 0.1 mM 4-AP +/- 5 mM Ca++ had no effect on stereospecific opiate binding, indicating that the antagonist actions of these agents in our cultures do not occur at the level of the opiate receptor. The relevance of our in vitro studies of 4-AP antagonism of opiate-depressant effects on sensory-evoked dorsal-horn network responses for analyses of problems in opiate analgesia has been strengthened by a recent report demonstrating that 4-AP does, in fact, reverse morphine analgesia in rats, as determined by tail flick tests.

4-Aminopyridine↗
PubMed1982

Development of cross-tolerance to 5-hydroxytryptamine in organotypic cultures of mouse spinal cord-ganglia during chronic exposure to morphine.

Exposure of organotypic explants of mouse spinal cord with attached dorsal root ganglia (DRGs) to low concentrations (approximately 10nM) of 5-hydroxytryptamine (5-HT) markedly depressed sensory-evoked dorsal-horn network responses, resembling the acute effects of opioids in these cultures. Attenuation of cord responses by 5-HT was not prevented by exposure to the 5-HT antagonists, methysergide and cyproheptadiene, nor to the opiate antagonist, naloxone. Explants that had become tolerant to morphine after chronic exposure (1 microM) for greater than 2 days often developed cross-tolerance to 5-HT. Acute exposure of morphine-tolerant explants to naloxone (1 microM) further attenuated the effects of 5-HT so that the minimum depressant levels of 5-HT were often increased up to 30-fold. Increasing the extra-cellular Ca++ concentration (to 5 mM) and/or introduction of 4-aminopyridine markedly antagonized the depressant effects of 5-HT on DRG-evoked cord responses, so that 5-HT levels comparable to those used on morphine-tolerant explants were required to depress naive explants. These depressant effects of 5-HT on cord-DRG explants are consonant with antinociceptive actions of 5-HT administered to dorsal cord in situ. Our data suggest that 5-HT may block neuronal components of dorsal horn networks at similar regions to those that are depressed by opiates, i.g. presynaptic DRG nerve terminals where abundant opiate receptors are located. The marked attenuation of the depressant effects of both 5-HT and opiates on cord-DRG explants by high Ca++ raises the possibility that cross-tolerance to 5-HT in morphine-tolerant explants may result from the same neuronal alterations that render dorsal-horn networks tolerant to opiates. Furthermore, the increased degree of cross-tolerant cultures may be an expression of opiate dependence.

4-Aminopyridine↗
PubMedDate not supplied

Magnetic resonance imaging evidence of hippocampal sclerosis in progression: a case report.

A 32-month-old child presented in status epilepticus (SE) involving the left side of the body. Fast spin-echo magnetic resonance imaging (FSE-MRI) with hippocampal volumetry performed < or = 24 h after the seizure showed increased T2 signal of the right hippocampus, but no atrophy. Complex partial seizures (CPS) appeared at age 33 months, and three more episodes of SE occurred between 33 and 37 months of age. Follow-up FSE-MRI at 34 and at 45 months of age demonstrated progressive hippocampal atrophy with resolution of the increased T2 signal. Her CPS became intractable and, at age 51 months, she underwent right temporal lobectomy. In the ensuing 5 months, she has had only one major motor seizure. This case demonstrates that acute increased hippocampal T2 signal intensity can occur soon after SE and hippocampal sclerosis (HS) may become evident within months in the setting of recurrent early childhood SE. This observation may support the hypothesis that early childhood SE can lead to HS. Furthermore, this case suggests that years of temporal lobe CPS may not be necessary for development of HS.

Brain Diseases↗
PubMedDate not supplied

Familial Alzheimer's disease and cortical Lewy bodies: is there a genetic susceptibility factor?

The reason for the occurrence of Lewy body disease (LBD) in Alzheimer's disease (AD) patients is unknown. If brains from etiologically different AD groups differ in their tendency to develop cortical Lewy bodies, the concurrence of LBD in AD patients may be a manifestation of the AD process in specific AD subsets. To address this issue, we counted cortical Lewy bodies in AD patients with genetic abnormalities on chromosome 14 (n = 19), and chromosome 21 (n = 3), sporadic AD (n = 27), Down's syndrome (n = 1) and control (n = 26) patients. Cortical Lewy bodies were occasionally present in AD patients with long-duration disease in most of the above AD subgroups, but were not present in any of our age-matched control cases. We suggest that cortical Lewy body formation may be an intrinsic part of the late pathologic changes of AD regardless of etiology and that it is not specific to any of the AD subtypes studied.

Aged↗